The present invention relates to a method of fertility control in the human female by adherence to a novel oral contraceptive regimen. The regimen includes the administration of a combination of an estrogen and a progestogen during certain days of the reproductive cycle, and the administration of only the progestogen on certain of the other days of the cycle.
Research and development in the area of human contraception or fertility control has heretofore concentrated almost exclusively on preventative methods, whether in the form of chemical or physical diversions of or barriers to sperm transport, e.g., vaginal creams and foams, condoms, diaphragms, and intrauterine devices, or in the form of chemically based oral contraceptive. The former methods have been largely supplanted by the use of oral contraceptives which have proven to be extremely effective in the prevention of conception. This effectiveness, however, necessarily requires the administration of the oral contraceptive tablets over approximately 21 days of each reproductive cycle. During the remaining 7 days of the 28 day cycle, no hormone-containing tablets are given and it is during this period, if the reproductive cycle is accurately regulated, that normal menstrual flow takes place.
The most common form of oral contraception is based upon the daily administration of a combination of estrogen and progestogen substances for about 21 successive days, starting generally on the 5th day of the menstrual cycle. After the 21 day period, there follows a 7 day period during which neither the estrogen or progestogen substances are taken. If the reproductive cycle of the female has been properly regulated, the normal and characteristic menstrual flow is supposed to, and generally does, occur within the 7 day period.
A second method which has been developed is the "sequential" system wherein from the 5th through about the 19th day of the cycle only an estrogen is given. A different tablet containing both estrogen and progestogen substances is given for the 5 days from the 20th to the 24th day of the cycle. This regimen more closely approximates the time-related secretion by the female body of its own reproductive cycle-controlling hormones. As with the combined treatment, there are no hormonal substances given during the 7 days following the 24th day. If the reproductive cycle has been properly regulated, the normal menstrual flow will, and generally does, occur within the 7 day period.
Although oral contraceptives have proven to be extremely effective in controlling fertility, the administration of oral contraceptive formulations, like other potent drugs, has some side effects. Since the oral contraceptives maintain a pseudopregnancy condition, the most commonly occuring side effects are similar to the common symptoms observed during pregnancy. Such side effects may be attributable to the potent estrogenic and progestogenic agents administered during the course of the regimen. Accordingly, it is of continuing interest to those in this field to develop new oral contraceptive regimens which control fertility, yet do so with lower dosages of estrogen and/or progestogen agents, minimized side effects, or do so in an improved manner.
Thus, Coutinho and deSouza, J. Reprod. Fert.16,137-139, (1968) suggest the administration of a combined tablet containing estrogen and progestogen every other day starting on the 5th day of the menstrual cycle and ending on the 23rd day of the cycle. On intervening days between the 5th and the 23rd days of the cycle, no tablets or placebos are administered. Although it was concluded that the contraceptive effectiveness of such a regimen is unaltered by extending the interval of administration to alternate days (as opposed to administration on 21 consecutive days), the reported data also shows that this was achieved with some sacrifice in cycle regulation and duration of menstrual flow. Specifically, regulation of the reproductive cycle to give menstrual flow upon termination of medication (i.e., so called "withdrawal bleeding") was only effective in slightly over 50% of the cycles recorded. This loss of cycle regulation can, in turn, expose the patient to the possibility of conception during an "unprotected" period (i.e., where no active medication is being taken) which does not coincide with actual menstrual flow. Additionally, the complete absence of menstrual flow (i.e. amenorrhoea) increased significantly as did those instances where the duration of menstrual flow was undesirably long (i.e., greater than 8 days).